For a number of years we have been investigating the cytochrome P-450 monooxygenase systems (P-450 systems) of rabbit liver and lung. The results of these studies have provided explanations for some of the differences that have been noted between the abilities of these two tissues to metabolize xenobiotics. The key to these explanations has been the discovery that the concentrations and types of cytochrome P-450 isozymes present in liver and lung differ significantly. At present we are primarily concerned with the distribution of cytochrome P-450, form 5, in liver and lung and its response to various inducers and repressors. Until recently, the evidence for isozyme 5 in the liver could be obtained only by immunochemical methods. Now, however, this enzyme has been purified from the livers of rabbits treated with phenobarbital. A direct comparison of isozyme 5 from liver and lung can now be carried out. This structural, immunochemical and catalytic comparison should provide information sufficient to establish if these proteins are identical. The second major isozyme of rabbit lung, form 2, is also under investigation. The results of our previous work have not provided any evidence that the liver and lung enzymes are different. However, we now have some evidence that microheterogenous forms of isozyme 2 may exist in the liver but not in the lung. The immunochemical techniques now available make detailed investigations of the P-450 systems of tissues other than liver and lung (the two tissues with the highest concentrations of cytochrome P-450) possible. Because one of the isozymes (form 5) studies in our laboratory is highly active in the metabolism of aromatic amines, we have initiated an investigation of the P-450 system of rabbit bladder, the target tissue for the carcinogenic effects of these compounds. Rabbit bladder contains isozymes 2, 5 and 6 but does not contain isozyme 4. Therefore, the bladder has the enzyme required for the metabolism of aromatic amines to reactive products. Like the lung, however, the bladder has little or no ability to N-hydroxylate 2-acetylaminofluorene and can activate this compound only after it has been deacetylated to 2-aminofluorene.